Third-world medicine

Hale and healthy

A new way of developing drugs for neglected diseases of the poor world

THIS week, scientists from the Institute for OneWorld Health, the first not-for-profit pharmaceutical company in America, presented the results of a large clinical trial at the Third World Congress on Leishmaniasis in Palermo, Italy. Leishmaniasis is a parasitic infection transmitted by the bite of a sand fly. The trial shows that an antibiotic called paromomycin is effective for treating the most dangerous version of the disease, visceral leishmaniasis, which affects 1.5m people around the world and kills 200,000 of them every year. Those data are obviously important for medical reasons. But they are also important as a demonstration that the institute's novel approach to drug development is working.

About 90% of the planet's disease burden falls on the developing world. Yet only 3% of the research and development expenditure of the pharmaceutical industry is directed toward those ailments. The rest goes towards treating diseases of the rich. In 2000, Victoria Hale (pictured above), founded the institute to help tackle that discrepancy. She knew from her work as a scientist in the pharmaceutical and biotechnology industries, and subsequently as an official at America's Food and Drug Administration, that numerous promising drug-development projects—particularly for diseases of the poor—are dropped for lack of funding. She reasoned that there was a gap in the market, between academically inclined university departments and fully fledged pharmaceutical firms, for an organisation that would identify such orphans, get their owners to donate the intellectual property if they were still in patent, raise development funding from non-commercial sources, and arm-twist researchers to contribute their expertise to the development process pro bono.

So far, the donation side seems to have worked. In 2002 Celera Genomics gave the institute a promising compound for the treatment of Chagas disease, which infects 12m people in Latin America and is an important cause of heart failure in the region. Yale University has also licensed a potential drug for Chagas to the institute. And the University of California, Santa Barbara, gave it a compound intended for the treatment of schistosomiasis, which affects 200m people, mostly in sub-Saharan Africa. The compound the institute has pushed furthest, though, is paromomycin. In this case no donation was needed, as the drug's patent has expired. Indeed, it is currently used for the treatment of a variety of parasites. But it has never been properly road-tested for leishmaniasis.

Trials and tribulations

Visceral leishmaniasis occurs predominantly in Bangladesh, Brazil, India, Nepal and Sudan. Its symptoms include fever, weight loss, enlargement of the spleen and liver, and anaemia. Several drugs to treat it are available, but their usefulness is limited either because the parasites have evolved resistance to them, or because they are too expensive.

In the mid-1990s, the World Health Organisation (WHO) started testing an injectable form of paromomycin as a treatment for visceral leishmaniasis. Its researchers completed small-scale trials which demonstrated that the drug was safe for use against the disease and seemed to cure the infection. But development stalled at that point because the WHO was unable to find a sponsor for a large-scale trial that would have compared paromomycin with existing treatments.

In 2001, Dr Hale approached the WHO about taking over the trials. The WHO agreed, the Bill and Melinda Gates Foundation stumped up the money, and the institute teamed up with four health-care centres in the Indian state of Bihar in order to test the drug against amphotericin B, an established but expensive treatment.

The trial showed that the two drugs worked more or less equally well. In both cases, 99% of patients responded within four weeks—and though slightly fewer of those on paromomycin remained uninfected after six months, all those relapses proved treatable by other drugs. Given that a course of amphotericin B costs $120, while the institute reckons a course of paromomycin will come in at around $10, this seems a reasonable trade-off. The institute, supported by a further donation from the Gates foundation, plans to submit an application for regulatory approval to the Indian health ministry by the end of the year. If that is granted, the manufacturing will be done by Gland Pharma, a drug company based in Hyderabad.

Having shown its approach can work, the institute's next target is diarrhoea, which kills 2m people a year, most of them children, by dehydrating them. In this case, the Lehman Brothers Foundation is providing the money.

Diarrhoea is a symptom, rather than a disease. Indeed, it has eight common causes in the tropics (four bacteria, three viruses and a protozoan). Instead of scattering its efforts among these causes, the institute's researchers are sifting through orphan compounds that might attack dehydration directly, by stopping the secretion of water into the gut. Such a drug would augment oral rehydration therapy—a combination of salt and sugars mixed into water that is the standard regimen used in the developing world. Diarrhoea is hardly the most glamorous condition it is possible to work on. But if Dr Hale and her institute can find a treatment for it among other people's discards, they will truly have turned base metal into gold.